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Gut peptide changes in patients with obstructive jaundice undergoing biliary drainage:A prospective case control study

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World Journal of Clinical Cases 2022年第17期10卷 5551-5565页

作者： Tajana Pavic Stipe Pelajic Nina Blazevic Dominik Kralj Milan Milosevic ivana mikolasevic Ivan Lerotic Davor Hrabar Department of Gastroenterology and Hepatology University Hospital Center Sestre MilosrdniceZagreb 10000Croatia Andrija Stampar School of Public Health WHO Collaborative Centre for Occupational Health University of ZagrebSchool of MedicineZagreb 10000Croatia Department of Gastroenterology University Hospital Center RijekaRijeka 51000Croatia

BACKGROUND Biliary obstruction is a relatively common condition that affects approximately 5 in 1000 people annually.Malnutrition is very common in patients with biliary obstruction and since it is associated with significant morbidity and mortality,it is important to identify factors and mechanisms involved in its development.AIM To determine the influence of obstructive jaundice on the hormones controlling appetite and nutritive status.METHODS This was a prospective case control study performed in a tertiary center in Zagreb,Croatia.Patients with biliary obstruction undergoing internal biliary drainage from September 2012 until August 2013 were enrolled.After excluding patients who developed procedure related complications or were lost in the follow-up,out of initial 73 patients,55 patients were included in the analysis,including 34 with benign and 21 with malignant disease.Meanwhile,40 non-jaundiced controls were also included.Appetite,nutritional status,and serum ghrelin,cholecystokinin(CCK),interleukin 6(IL-6),and tumor necrosis factorα(TNF-α)were determined at admission,48 h and 28 d after internal biliary drainage.Chi square test was used for categorical variables.Continuous variables were analysed for normality by Kolmogorov-Smirnov test and relevant non-parametric(Mann-Whitney,Kruskal-Wallis,and Friedman)or parametric(t-test and analysis of variance)tests were used.RESULTS Patients with obstructive jaundice were significantly malnourished compared to controls,regardless of disease etiology.Plasma ghrelin and CCK levels were significantly higher in patients with obstructive jaundice.Serum bilirubin concentrations were negatively correlated with ghrelin levels and positively correlated with TNF-α,but had no correlation with CCK concentrations.After internal biliary drainage,a significant improvement of nutritional status was observed although serum concentrations of ghrelin,IL-6,and TNF-α remained significantly elevated even 28 d after the procedure.CCK levels in patients without malnutrition remained elev

关键词： Ghrelin Cholecystokinin Biliary obstruction Malnutrition

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Liver regeneration as treatment target for severe alcoholic hepatitis

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World Journal of Gastroenterology 2022年第32期28卷 4557-4573页

作者： Lucija Virovic-Jukic Dominik Ljubas Sanja Stojsavljevic-Shapeski Neven Ljubičić Tajana Filipec Kanizaj ivana mikolasevic Ivica Grgurevic Department of Gastroenterology and Hepatology Sisters of Charity University Hospital CenterZagreb 10000Croatia Department of Internal Medicine University of Zagreb School of MedicineZagreb 10000Croatia Department of Internal Medicine University of Zagreb School of Dental MedicineZagreb 10000Croatia Department of Gastroenterology Merkur University HospitalZagreb 10000Croatia Department of Gastroenterology Rijeka University Hospital CenterRijeka 51000Croatia Department of Internal Medicine University of Rijeka School of MedicineRijeka 10000Croatia Department of Gastroenterology Hepatology and Clinical NutritionDubrava University HospitalZagreb 10000Croatia

Severe alcoholic hepatitis(AH)is a distinct entity in the spectrum of alcoholrelated liver disease,with limited treatment options and high mortality.Supportive medical care with corticosteroids in selected patients is the only currently available treatment option,often with poor outcomes.Based on the insights into the pathogenetic mechanisms of AH,which are mostly obtained from animal studies,several new treatment options are being explored.Studies have implicated impaired and deranged liver regeneration processes as one of the culprit mechanisms and a potential therapeutic target.Acknowledging evidence for the beneficial effects of granulocyte colony-stimulating factor(G-CSF)on liver regeneration and immunomodulation in animal models,several human studies investigated its role in the treatment of advanced alcohol-related liver disease and AH.Contrary to the previously published studies suggesting benefits of G-CSF in the outcomes of patients with severe AH,these effects were not confirmed by a recently published multicenter randomized trial,suggesting that other options should rather be pursued.Stem cell transplantation represents another option for improving liver regeneration,but evidence for its efficacy in patients with severe AH and advanced alcohol-related liver disease is still very scarce and unconvincing,with established lack of efficacy in patients with compensated cirrhosis.In this review,we summarize the current knowledge on the pathogenesis and experimental therapies targeting liver regeneration.The lack of high-quality studies and evidence is a major obstacle in further treatment development.New insights into the pathogenesis of not only liver injury,but also liver regeneration processes are mandatory for the development of new treatment options.A reliable experimental model of the pathogenesis of AH and processes involved in liver recovery is still missing,and data obtained from animal studies are essential for future research.

关键词： Severe alcoholic hepatitis Alcohol-related liver disease Treatment Liver regeneration Granulocyte colony-stimulating factor Stem cell transplantation

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Advances in diagnosis of chronic liver diseases in pediatric patients

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World Journal of Pediatrics 2018年第6期14卷 541-547页

作者： Lucija Ruzman ivana mikolasevic Kristina Baraba Dekanic Sandra Milic Goran Palcevski Pediatric Clinic UHC RijekaIstarska 4351000 RijekaCroatia Department of Gastroenterology UHC RijekaRijekaCroatia Pediatric Clinic Department of GastroenterologyUHC RijekaRijekaCroatia

Background Chronic liver diseases (CLD) present important clinical problem in children with various age-dependent causes. Nonalcoholic fatty liver disease (NAFLD) with its increasing prevalence is a major problem with regard to its timely recog-nition and the need for long-term disease monitoring. At present, a perfect non-invasive method for the evaluation of liver fibrosis is not available. Methods A non-systematic literature search was performed to summarize the current knowledge about transient elastog-raphy (TE) with controlled attenuation parameter (CAP) in children with CLD. Ovid MEDLINE, Ovid EMBASE, Google scholar, and The Cochrane Library databases were searched for relevant articles evaluating TE in the pediatric population. Results Normal values of liver stiffness measurements (LSM) according to the age are given, as well as the advantages and disadvantages of the method. The utility of TE in specific liver disease in pediatric population is summarized. Conclusions TE with CAP is a valuable non-invasive method for the liver-damage assessment. Clinical interpretation of TE results should be made in parallel with the assessment of the patient's demographics, disease etiology, and essential laboratory parameters.

关键词： Child Liver disease Liver stiffness Pediatric Transient elastography

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Nonalcoholic fatty liver disease-A multisystem disease?

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World Journal of Gastroenterology 2016年第43期22卷 9488-9505页

作者： ivana mikolasevic Sandra Milic Tamara Turk Wensveen ivana Grgic Ivan Jakopcic Davor Stimac Felix Wensveen Lidija Orlic Department of Gastroenterology UHC Rijeka51000 Rijeka Croatia Department of Endocrinology Diabetes and Metabolic Diseases UHC Rijeka51000 Rijeka Croatia Department of Cardiology UHC Rijeka51000 Rijeka Croatia School of Medicine 51000 Rijeka Croatia Department of Histology and Embryology School of Medicine51000 Rijeka Croatia Department of Nephrology Dialysis and Kidney Transplantation UHC Rijeka51000 Rijeka Croatia

Non-alcoholic fatty liver disease(NAFLD) is one of the most common comorbidities associated with overweight and metabolic syndrome(Met S). Importantly, NAFLD is one of its most dangerous complications because it can lead to severe liver pathologies, including fibrosis, cirrhosis and hepatic cellular carcinoma. Given the increasing worldwide prevalence of obesity, NAFLD has become the most common cause of chronic liver disease and therefore is a major global health problem. Currently, NAFLD is predominantly regarded as a hepatic manifestation of Met S. However, accumulating evidence indicates that the effects of NAFLD extend beyond the liver and are negatively associated with a range of chronic diseases, most notably cardiovascular disease(CVD), diabetes mellitus type 2(T2DM) and chronic kidney disease(CKD). It is becoming increasingly clear that these diseases are the result of the same underlying pathophysiological processes associated with Met S, such as insulin resistance, chronic systemic inflammation and dyslipidemia. As a result, they have been shown to be independent reciprocal risk factors. In addition, recent data have shown that NAFLD actively contributes to aggravation of the pathophysiology of CVD, T2 DM, and CKD, as well as several other pathologies. Thus, NAFLD is a direct cause of many chronic diseases associated with MetS, and better detection and treatment of fatty liver disease is therefore urgently needed. As non-invasive screening methods for liver disease become increasingly available, detection and treatment of NAFLD in patients with MetS should therefore be considered by both(sub-) specialists and primary care physicians.

关键词：不含酒精的脂肪肝疾病新陈代谢的症候群糖尿病 mellitus 类型 2 心血管的疾病长期的肾疾病 Multisystem 疾病

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Endoscopic retrograde cholangiopancreatography-induced and non-endoscopic retrograde cholangiopancreatographyinduced acute pancreatitis:Two distinct clinical and immunological entities?

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World Journal of Gastrointestinal Endoscopy 2018年第10期10卷 259-266页

作者： ivana Plavsic ivana Zitini ivana mikolasevic Goran Poropat Goran Hauser Department of Anesthesiology and Critical care medicine Clinical Hospital CentreMedical FacultyUniversity of RijekaRijeka 51000Croatia Department of Emergency Medicine Clinical Hospital CentreRijeka 51000Croatia Department of Internal Medicine Division of GastroenterologyClinical Hospital CentreMedical FacultyUniversity of RijekaRijeka 51000Croatia Department of Internal Medicine Division of GastroenterologyClinical Hospital CentreMedical FacultyFaculty of health StudiesUniversity of RijekaRijeka 51000Croatia

Acute pancreatitis(AP) is common gastrointestinal disease of varied aetiology. The most common cause of AP is gallstones, followed by alcohol abuse as an independent risk factor. With the increased need for invasive techniques to treat pancreatic and bile duct pathologies such as endoscopic retrograde cholangiopancreatography(ERCP), AP has emerged as the most frequent complication. While severe AP following ERCP is rare(0.5%), if it does develop it has a greater severity index compared to non-ERCP AP. Development of a mild form of AP after ERCP is not considered a clinically relevant condition. Differences in the clinical presentation and prognosis of the mild and severe forms have been found between non-ERCP AP and postendoscopic pancreatitis(PEP). It has been proposedthat AP and PEP may also have different immunological responses to the initial injury. In this review, we summarise the literature on clinical and inflammatory processes in PEP vs non-ERCP AP.

关键词： Acute pancreatitis Endoscopic retrograde cholangiopancreatography Post endoscopic retrograde cholangiopancreatography pancreatitis

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Nonalcoholic fatty liver disease and liver transplantation-Where do we stand?

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World Journal of Gastroenterology 2018年第14期24卷 1491-1506页

作者： ivana mikolasevic Tajana Filipec-Kanizaj Maja Mijic Ivan Jakopcic Sandra Milic Irena Hrstic Nikola Sobocan Davor Stimac Patrizia Burra Department of Gastroenterology UHC Rijeka School of Medicine University of Rijeka Department of Gastroenterology University Hospital MerkurSchool of Medicine University of Zagreb Department of Internal medicine General Hospital Pula Pula School of Medicine University of Rijeka and Zagreb Multivisceral Transplant Unit Department of Surgery Oncology and Gastroenterology Padua University Hospital

Nonalcoholic fatty liver disease/nonalcoholic steatohepatitis(NAFLD/NASH) is a challenging and multisystem disease that has a high socioeconomic impact. NAFLD/NASH is a main cause of macrovesicular steatosis and has multiple impacts on liver transplantation(LT), on patients on the waiting list for transplant, on posttransplant setting as well as on organ donors. Current data indicate new trends in the area of chronic liver disease. Due to the increased incidence of metabolic syndrome(Met S) and its components, NASH cirrhosis and hepatocellular carcinoma caused by NASH will soon become a major indication for LT. Furthermore, due to an increasing incidence of Met S and, consequently, NAFLD, there will be more steatotic donor livers and less high quality organs available for LT, in addition to a lack of available liver allografts. Patients who have NASH and are candidates for LT have multiple comorbidities and are unique LT candidates. Finally, we discuss long-term grafts and patient survival after LT, the recurrence of NASH and NASH appearing de novo after transplantation. In addition, we suggest topics and areas that require more research for improving the health care of this increasing patient population.

关键词： nonalcoholic steatohepatitis chronic liver disease liver transplantation nonalcoholic fatty liver disease outcome

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Liver disease in the era of COVID-19: Is the worst yet to come?

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World Journal of Gastroenterology 2021年第36期27卷 6039-6052页

作者： ivana mikolasevic Dorotea Bozic Tajana Pavić Alen Ruzic Goran Hauser Marija Radic Delfa Radic-Kristo Melanija Razov-Radas Zeljko Puljiz Sandra Milic Department of Gastroenterology Clinical Hospital Center RijekaRijeka 51000Croatia Department of Gastroenterology University Hospital MerkurZagreb 10000Croatia Faculty of Medicine University of RijekaRijeka 51000Croatia Department for Gastroenterology and Hepatology University Hospital Center SplitSplit 21000Croatia Department of Gastroenterology and Hepatology Faculty of MedicineSestre Milosrdnice University Hospital CenterZagreb 10000Croatia Clinic for Cardiology University Hospital Center RijekaRijeka 51000Croatia Faculty of Health Studies University of RijekaRijeka 51000Croatia Faculty of Medicine Zagreb 10000Croatia Department of Hematology University Hospital MerkurZagreb 10000Croatia Division of Gastroenterology General Hospital ZadarZadar 23000Croatia University of Split School of MedicineSplit 21000Croatia

The global social,economic and political crises related to coronavirus disease 2019(COVID-19)presumably had more indirect than direct negative impacts on health systems.Drastic lifestyle changes,social isolation and distancing,and individual and global financial crises resulted in robust populations forfeiting healthy habits and seeking comfort in alcoholic beverages,drugs and unhealthy diets.The inevitable consequences are increases in the incidence of nonalcoholic fatty liver disease,viral hepatitis,acute alcoholic hepatitis,liver cirrhosis decompensation and ultimately liver-related mortality.The inaccessibility of regular clinical and sonographic monitoring systems has caused difficulties in the treatment of patients with chronic liver disease(CLD)and has prevented prompt hepatocellular carcinoma detection and treatment.A dramatic reduction in the number of liver donors and the transformation of numerous transplantation centers into COVID-19 units drastically decreased the rate of orthotopic liver transplantation.The indirect,unavoidable effects of the COVID-19 pandemic in the following years have yet to be determined.Substantial efforts in the management of patients with liver disease in order to overcome the inevitable COVID-19-related morbidity and mortality that will follow have yet to be initiated.Several questions regarding the impact of the COVID-19 pandemic on liver disease remain.The most important question for general CLD patients is:How will the modification of clinical practice during this pandemic affect the outcomes of CLD patients?This article reviews the influence of COVID-19 on patients with liver disease during the pandemic,with particular emphasis on the disease course associated with pandemic resolution.

关键词： COVID-19 Pandemic Chronic liver disease Management Impact Liverrelated mortality

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Noninvasive markers of liver steatosis and fibrosis after liver transplantation-Where do we stand?

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World Journal of Transplantation 2021年第3期11卷 37-53页

作者： ivana mikolasevic Sanja Stojsavljevic Filip Blazic Maja Mijic Delfa Radic-Kristo Toni Juric Nadija Skenderevic Mia Klapan Andjela Lukic Tajana Filipec Kanizaj Department of Gastroenterology Clinical Hospital Centre RijekaRijekaCroatiaDepartment of GastroenterologyClinical hospital MerkurZagrebCroatiaFaculty of MedicineUniversity of RijekaRijekaCroatia Department of Gastroenterology University Hospital Center“Sestre Milosrdnice”Zagreb 10000Croatia Department of Gastroenterology University Hospital Center RijekaRijeka 51000Croatia Department of Gastroenterology University Hospital MerkurZagreb 10000Croatia Department of Hematology University Hospital MerkurZagrebCroatiaFaculty of MedicineUniversity of ZagrebZagrebCroatia School of Medicine School of MedicineRijeka 51000Croatia Department of Gastroenterology University Hospital MerkurZagrebCroatiaFaculty of MedicineUniversity of ZagrebZagrebCroatia

In the last two decades,advances in immunosuppressive regimens have led to fewer complications of acute rejection crisis and consequently improved shortterm graft and patient survival.In parallel with this great success,long-term posttransplantation complications have become a focus of interest of doctors engaged in transplant medicine.Metabolic syndrome(MetS)and its individual components,namely,obesity,dyslipidemia,diabetes,and hypertension,often develop in the post-transplant setting and are associated with immunosuppressive therapy.Nonalcoholic fatty liver disease(NAFLD)is closely related to MetS and its individual components and is the liver manifestation of MetS.Therefore,it is not surprising that MetS and its individual components are associated with recurrent or“de novo”NAFLD after liver transplantation(LT).Fibrosis of the graft is one of the main determinants of overall morbidity and mortality in the post-LT period.In the assessment of post-LT steatosis and fibrosis,we have biochemical markers,imaging methods and liver biopsy.Because of the significant economic burden of post-LT steatosis and fibrosis and its potential consequences,there is an unmet need for noninvasive methods that are efficient and cost-effective.Biochemical scores can overestimate fibrosis and are not a good method for fibrosis evaluation in liver transplant recipients due to frequent post-LT thrombocytopenia.Transient elastography with controlled attenuation parameter is a promising noninvasive method for steatosis and fibrosis.In this review,we will specifically focus on the evaluation of steatosis and fibrosis in the post-LT setting in the context of de novo or recurrent NAFLD.

关键词： Steatosis Fibrosis Noninvasive methods Transient elastography Transplantation Nonalcoholic fatty liver disease

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Transient elastography(Fibro Scan~?) with controlled attenuation parameter in the assessment of liver steatosis and fibrosis in patients with nonalcoholic fatty liver disease- Where do we stand?

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World Journal of Gastroenterology 2016年第32期22卷 7236-7251页

作者： ivana mikolasevic Lidija Orlic Neven Franjic Goran Hauser Davor Stimac Sandra Milic Department of Gastroenterology UHC Rijeka Department of Nephrology Dialysis and Kidney Transplantation UHC Rijeka

Non-alcoholic fatty liver disease(NAFLD) is the most common cause of chronic liver disease worldwide. Currently, the routinely used modalities are unable to adequately determine the levels of steatosis and fibrosis(laboratory tests and ultrasonography) or cannot be applied as a screening procedure(liver biopsy). Among the non-invasive tests, transient elastography(Fibro Scan?, TE) with controlled attenuation parameter(CAP) has demonstrated good accuracy in quantifying the levels of liver steatosis and fibrosis in patients with NAFLD, the factors associated with the diagnosis and NAFLD progression. The method is fast, reliable and reproducible, with good intra- and interobserver levels of agreement, thus allowing for population-wide screening and disease follow-up. The initial inability of the procedure to accurately determine fibrosis and steatosis in obese patients has been addressed with the development of the obese-specific XL probe. TE with CAP is a viable alternative to ultrasonography, both as an initial assessment and during follow-up of patients with NAFLD. Its ability to exclude patients with advanced fibrosis may be used to identify low-risk NAFLD patients in whom liver biopsy is not needed, therefore reducing the risk of complications and the financial costs.

关键词： Non-alcoholic fatty liver disease Transient elastography Controlled attenuation parameter

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